The function of the Nef protein encoded by HIV and simian immunodeficiency virus (SIV) is still unknown. Several reports propose that they are involved in viral latency due to a negative effect on viral transcription. Frequent inactivating mutations in the gene occurring during virus isolation suggest that the gene is not tolerated well during propagation in tissue culture. In order to investigate the function of this gene we have extended our screen of animals infected with different isolates of SIV to see whether the appearance of the anti-nef response has a prognostic value for disease progression as has been reported in the case of HIV and human AIDS.